RESUMEN
BACKGROUND: Targeting long non-coding RNAs (LncRNAs) is a novel and promising approach in cancer therapy. In our previous study, we investigated the effects of ailanthone (aila), the main active compound derived from the stem barks of Ailanthus altissima (Mill.) Swingle, on the growth of non-small cell lung cancer (NSCLC) cells. Although we observed significant inhibition of NSCLC cell growth of aila, the underlying mechanisms involving LncRNAs, specifically LncRNA growth arrest specific 5 (GAS5), remain largely unknown. METHODS: To further explore the impact of aila on NSCLC, we performed a series of experiments. Firstly, we confirmed the inhibitory effect of aila on NSCLC cell growth using multiple assays, including MTT, wound healing, transwell assay, as well as subcutaneous and metastasis tumor mice models in vivo. Next, we utilized cDNA microarray and RT-QPCR to identify GAS5 as the primary target of aila. To verify the importance of GAS5 in aila-induced tumor inhibition, we manipulated GAS5 expression levels by constructing GAS5 over-expression and knockdown NSCLC cell lines. Furthermore, we investigated the upstream and downstream signaling pathways of GAS5 through western blot and RT-QPCR analysis. RESULTS: Our results showed that aila effectively increased GAS5 expression, as determined by microarray analysis. We also observed that aila significantly enhanced GAS5 expression in a dose- and time-dependent manner across various NSCLC cell lines. Notably, over-expression of GAS5 led to a significant suppression of NSCLC cell tumor growth; while aila had minimal inhibitory effect on GAS5-knockdown NSCLC cells. Additionally, we discovered that aila inhibited ULK1 and autophagy, and this inhibition was reversed by GAS5 knockdown. Moreover, we found that aila up-regulated GAS5 expression by suppressing UPF1-mediated nonsense-mediated mRNA decay (NMD). CONCLUSION: In summary, our findings suggest that aila promotes GAS5 expression by inhibiting UPF1-mediated NMD, leading to the repression of ULK1-mediated autophagy and subsequent inhibitory effects on NSCLC cells. These results indicate that aila is a potent enhancer of GAS5 and holds promising potential for application in NSCLC therapy. However, our research is currently focused only on NSCLC. It remains to be determined whether aila can also inhibit the growth of other types of tumors through the UPF1/GAS5/ULK1 signaling pathway. In future studies, we can further investigate the mechanisms by which aila suppresses other types of tumors and potentially broaden the scope of its application in cancer therapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , ARN Largo no Codificante , Transducción de Señal , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , ARN Largo no Codificante/genética , Humanos , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ratones , Ratones Desnudos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Transactivadores/genética , Transactivadores/metabolismo , Ailanthus/química , Antineoplásicos Fitogénicos/farmacología , Ratones Endogámicos BALB C , Cuassinas/farmacología , ARN Helicasas/metabolismoRESUMEN
Hyperuricemia (HUA) is a prevalent chronic disease, characterized by excessive blood uric acid levels, that poses a significant health risk. In this study, the preventive effects and potential mechanisms of ethanol extracts from Chinese sumac (Rhus chinensis Mill.) fruits on HUA and uric acid nephropathy were comprehensively investigated. The results demonstrated a significant reduction in uric acid levels in hyperuricemia mice after treatment with Chinese sumac fruit extract, especially in the high-dose group, where the blood uric acid level decreased by 39.56%. Visual diagrams of the kidneys and hematoxylin and eosin (H&E)-stained sections showed the extract's effectiveness in protecting against kidney damage caused by excessive uric acid. Further investigation into its mechanism revealed that the extract prevents and treats hyperuricemia by decreasing uric acid production, enhancing uric acid excretion, and mitigating the oxidative stress and inflammatory reactions induced by excessive uric acid in the kidneys. Specifically, the extract markedly decreased xanthine oxidase (XOD) levels and expression in the liver, elevated the expression of uric acid transporters ABCG2, and lowered the expression of uric acid reabsorption proteins URAT1 and SLC2A9. Simultaneously, it significantly elevated the levels of endogenous antioxidant enzymes (SOD and GSH) while reducing the level of malondialdehyde (MDA). Furthermore, the expression of uric-acid-related proteins NLRP3, ACS, and Caspase-3 and the levels of IL-1ß and IL-6 were significantly reduced. The experimental results confirm that Chinese sumac fruit extract can improve HUA and uric acid nephropathy in mice fed a high-purine yeast diet. This finding establishes a theoretical foundation for developing Chinese sumac fruit as a functional food or medicine for preventing and treating HUA.
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Ailanthus , Hiperuricemia , Enfermedades Renales , Rhus , Animales , Ratones , Saccharomyces cerevisiae , Frutas , Ácido Úrico , Hiperuricemia/inducido químicamente , Hiperuricemia/prevención & control , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Extractos Vegetales/farmacología , DietaRESUMEN
Structural characteristics-guided investigation of Ailanthus altissima (Mill.) Swingle resulted in the isolation and identification of seven undescribed potential Michael reaction acceptors (1-7). Ailanlactone A (1) possesses an unusual 1,7-epoxy-11,12-seco quassinoid core. Ailanterpene B (6) was a rare guaianolide-type sesquiterpene with a 5/6/6/6-fused skeleton. Their structures were determined through extensive analysis of physiochemical and spectroscopic data, quantum chemical calculations, and single crystal X-ray crystallographic technology using Cu Kα radiation. The cytotoxic activities of isolates on HepG2 and Hep3B cells were evaluated in vitro. Encouragingly, ailanaltiolide K (4) showed significant cytotoxicity against Hep3B cells with IC50 values of 1.41 ± 0.21 µM, whose covalent binding mode was uncovered in silico.
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Ailanthus , Cuassinas , Ailanthus/química , Extractos Vegetales/química , Hojas de la Planta , Cuassinas/químicaRESUMEN
BACKGROUND: The dried bark of Ailanthus altissima (Mill.) Swingle is widely used in traditional Chinese medicine for the treatment of ulcerative colitis. The objective of this study was to explore the therapeutic basis of the dried bark of Ailanthus altissima (Mill.) Swingle for the treatment of ulcerative colitis based on Virtual Screening-Molecular Docking-Activity Evaluation technology. METHODS: By searching the Traditional Chinese Medicine Systems Pharmacology TCMSP Database and Analysis Platform, 89 compounds were obtained from the chemical components of the dried bark of Ailanthus altissima (Mill.) Swingle. Then, after preliminarily screening the compounds based on Lipinski's rule of five and other relevant conditions, the AutoDock Vina molecular docking software was used to evaluate the affinity of the compounds to ulcerative colitis-related target proteins and their binding modes through use of the scoring function to identify the best candidate compounds. Further verification of the compound's properties was achieved through in vitro experiments. RESULTS: Twenty-two compounds obtained from the secondary screening were molecularly docked with ulcerative colitis-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energies of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins were - 8.7, - 8.0, - 9.2, - 7.7, and - 8.5 kcal/mol, respectively. The potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained through scoring function and docking mode analysis. Furthermore, the potential compound ailanthone (1, 3, and 10 µM) was found to have no significant effect on cell proliferation, though at 10 µM it reduced the level of pro-inflammatory factors caused by lipopolysaccharide. CONCLUSION: Among the active components of the dried bark of Ailanthus altissima (Mill.) Swingle, ailanthone plays a major role in its anti-inflammatory properties. The present study shows that ailanthone has advantages in cell proliferation and in inhibiting of inflammation, but further animal research is needed to confirm its pharmaceutical potential.
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Ailanthus , Colitis Ulcerosa , Humanos , Animales , Ailanthus/química , Simulación del Acoplamiento Molecular , Colitis Ulcerosa/tratamiento farmacológico , Corteza de la Planta/química , Receptores ErbBRESUMEN
Being vector of West Nile Virus and falariasis the control of Culex quinquefasciatus is likely to be essential. Synthetic insecticide treatment is looking most effective for vectors mosquito control. However, these products are toxic to the environment and non-target organisms. Consequently, ecofriendly control of vectors mosquito is needed. In this regard botanical insecticide is looking more fruitful. Therefore, the present research aimed to investigate the effectiveness of methanolic extract and various fractions, including, n-hexane, ethyl-acetate, chloroform, and aqueous fraction, obtained from methanolic extract of Ailanthus altissima, Artemisia scoparia, and Justicia adhatoda using separating funnel against larval, pupal, and adult stages of Culex quinquefasciatus. The larvae and pupae of Culex quinquefasciatus were exposed to various concentrations (31.25-1000 ppm) of methanolic extract and its fractions for 24 hours of exposure period. For knock-down bioassay (filter paper impregnation bioassay) different concentration of the methanolic extract and its various fractions (i.e. 0.0625, 0.125, 0.25, 0.5 and 1mg/mL) were applied for 1 hour exposure period. The results were statistically analysed using standard deviation, probit analysis, and linear regression. The R2 values of larvae, pupae, and adult range from 0.4 to 0.99. The values of LC50 (concentration causing 50% mortality) for late 3rd instar larvae after 24 hours exposure period range from 93-1856.7 ppm, while LC90 values range from 424 -7635.5ppm. The values of LC50for pupae range form 1326.7-6818.4ppm and and values of LC90 range from 3667.3-17427.9ppm, respectively. The KDT50 range from 0.30 to 2.8% and KDT90 values range from1.2 to 110.8%, respectively. In conclusion, Justicia adhatoda may be effective for controlling populations of vector mosquito.
Por ser o vetor do vírus do Nilo Ocidental e da falaríase, o controle de Culex quinquefasciatus Say é provavelmente essencial. O tratamento com inseticida sintético parece ser mais eficaz para o controle dos mosquitos vetores. No entanto, esses produtos são tóxicos para o meio ambiente e organismos não visados. Consequentemente, o controle ecológico dos mosquitos vetores é necessário. Nesse sentido, o inseticida botânico parece mais produtivo. Portanto, a presente pesquisa teve como objetivo investigar a eficácia do extrato metanólico e de várias frações, incluindo n-hexano, acetato de etila, clorofórmio e fração aquosa, obtidos do extrato metanólico de Ailanthus altissima (Mill.) Swingle, Artemisia scoparia Waldst. & Kit. e Justicia adhatoda L. usando funil de separação contra os estágios larval, pupal e adulto de C. quinquefasciatus. As larvas e pupas de C. quinquefasciatus foram expostas a várias concentrações (31,25-1000 ppm) de extrato metanólico, e suas frações por 24 horas de período de exposição. Para o bioensaio knock-down (bioensaio de impregnação de papel de filtro), diferentes concentrações do extrato metanólico e suas várias frações (ou seja, 0,0625, 0,125, 0,25, 0,5 e 1 mg / mL) foram aplicadas por um período de exposição de 1 hora. Os resultados foram analisados estatisticamente usando desvio padrão, análise Probit e regressão linear. Os valores de R2 de larvas, pupas e adultos variaram de 0,4 a 0,99. Os valores de LC50 (concentração que causa 50% de mortalidade) para larvas de terceiro estádio tardio após 24 horas de período de exposição variaram de 93-1856,7 ppm, enquanto os valores de LC90 variaram de 424-7635,5ppm. Os valores de LC50 para pupas variaram de 1326,7-6818,4 ppm e os valores de LC90 variaram de 3667,3-17427,9 ppm, respectivamente. O KDT50 variou de 0,30 a 2,8% e os valores de KDT90 variaram de 1,2 a 110,8%, respectivamente. Por fim, a espécie J. adhatoda pôde ser eficaz para controlar populações de mosquitos vetores.
Asunto(s)
Animales , Acanthaceae/química , Ailanthus/química , Artemisia/química , Control de Mosquitos , CulexRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear. AIM OF THE STUDY: In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS). MATERIALS AND METHODS: A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively. RESULTS: The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice. CONCLUSION: AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.
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Ailanthus/química , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Astrocitos/efectos de los fármacos , Astrocitos/patología , Citocinas/metabolismo , Inflamación/patología , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Óxido Nítrico/metabolismo , Extractos Vegetales/aislamiento & purificación , Hojas de la PlantaRESUMEN
Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.
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Apoptosis/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Piridinolcarbamato/metabolismo , Cuassinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Ailanthus/química , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Regulación hacia Abajo , Descubrimiento de Drogas , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Gástricas/metabolismo , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The dried bark of Ailanthus altissima (Mill.) Swingle (BAA), commonly designated as "Chunpi" in Chinese, is extensively used as a common traditional medicine in China, Korea, and India. It has been used to treat multiple ailments, including asthma, epilepsy, spermatorrhea, bleeding, and ophthalmic diseases, for thousands of years. AIM OF THE REVIEW: To present a comprehensive and constructive review on the phytochemistry, pharmacology, pharmacokinetics, traditional uses, quality control, and toxicology of BAA; to aid the assessment of the therapeutic potential of BAA; to guide researchers working on the development of novel therapeutic agents. MATERIALS AND METHODS: Information related to BAA (from 1960 to 2020) was retrieved from a wide variety of electronic databases, such as PubMed, Web of Science, China Knowledge Resource Integrated Database, ScienceDirect, SciFinder, and Google Scholar. Additional information and materials were acquired from Chinese Medicine Monographs, the 2020 edition of the Chinese Pharmacopoeia, and several web sources, such as the official website of The Plant List and Flora of China. Additionally, perspectives for future investigations and applications of BAA were extensively explored. RESULTS: Approximately 221 chemical compounds, including alkaloids, quassinoids, phenylpropanoids, triterpenoids, volatile oils, and other compounds, have been isolated and characterized from BAA; among these, the quassinoid ailanthone is the most typical. The crude extracts and active compounds of BAA have been reported to exert a wide range of pharmacological activities, such as antitumor, anti-inflammatory, antiviral, herbicidal, and insecticidal activities. Although BAA is safe when administered at a conventional dose, at higher doses, it exhibits toxicity due to the presence of quassinoids. Thus, more studies are required to evaluate the efficacy and safety of BAA. CONCLUSION: Modern pharmacological studies have revealed that BAA, as a valuable medicinal resource, possesses the potential to treat a wide variety of ailments, especially, cancer and gastrointestinal inflammation. These studies present a wide range of perspectives for the development of new drugs related to BAA. However, only a few traditional uses are associated with the reported pharmacological activities of BAA and have been confirmed by preclinical and clinical studies. Moreover, the pharmacokinetics, toxicology, and quality control of BAA should be considered indispensable research topics.
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Ailanthus/química , Medicina Tradicional/métodos , Corteza de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , China , Etnobotánica , Humanos , India , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitoquímicos/toxicidad , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Control de Calidad , República de CoreaRESUMEN
Two new benzoic acid derivatives (1-2), together with four known compounds (3-6) have been isolated from the n-BuOH soluble fraction of ethanolic extract from Ailanthus altissima. The gross structures of the new compounds were deduced by detailed spectroscopic analysis including HRESIMS and 1D/2D NMR spectroscopy. The stereochemistry of 1 was determined by modified Mosher's method. All compounds were evaluated for their neuroprotective effects against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells and none of them displayed obvious neuroprotective activities. [Formula: see text].
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Ailanthus , Ácido Benzoico , Peróxido de Hidrógeno/farmacología , Estructura Molecular , Extractos VegetalesRESUMEN
Phytochemistry investigations on Ailanthus altissima (Mill.) Swingle, a Simaroubaceae plant that is recognized as a traditional herbal medicine, have afforded various natural products, among which C20 quassinoid is the most attractive for their significant and diverse pharmacological and biological activities. Our continuous study has led to the isolation of two novel quassinoid glycosides, named chuglycosides J and K, together with fourteen known lignans from the samara of A. altissima. The new structures were elucidated based on comprehensive spectra data analysis. All of the compounds were evaluated for their anti-tobacco mosaic virus activity, among which chuglycosides J and K exhibited inhibitory effects against the virus multiplication with half maximal inhibitory concentration (IC50) values of 56.21 ± 1.86 and 137.74 ± 3.57 µM, respectively.
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Ailanthus/química , Antivirales/farmacología , Glicósidos/farmacología , Nicotiana/efectos de los fármacos , Extractos Vegetales/farmacología , Cuassinas/química , Virus del Mosaico del Tabaco/efectos de los fármacos , Lignanos/farmacología , Corteza de la Planta/química , Nicotiana/virologíaRESUMEN
Bark and leaves of Ailanthus altissima (Mill.) Swingle are widely used in European folk medicine to treat intestinal worm infections. The study aimed to rationalize a potential anthelmintic effect of A. altissima extract against the model organism Caenorhabditis elegans. A methanol-water (7:3, v/v) extract of the primary stem bark was tested on L4 larvae of C. elegans for induction of mortality and influence on reproduction. Bioactivity-guided fractionation was performed by chromatography on MCI-gel, preparative HPLC on RP18 stationary phase and fast-centrifugal-partition-chromatography. Structural elucidation of isolated quassinoids was performed by NMR and HR-ESI-MS. The sterilizing effect on C. elegans was investigated by light microscopy and atomic force microscopy of ultra-sections. Different GFP-tagged reporter strains were used to identify involved signaling pathways. A. altissima extract (1 mg/mL) irreversibly inhibited the reproduction of C. elegans L4 larvae. This effect was dependent on the larval stage since L3 larvae and adults were less affected. Bioactivity-guided fractionation revealed the quassinoid ailanthone 1 as the major active compound (IC50 2.47 µM). The extract caused severe damages to germ cells and rachis, which led to none or only poorly developed oocytes. These damages led to activation of the transcription factor DAF-16, which plays a major role in the nematode's response to stress. A regulation via the respective DAF-2/insulin-like signaling pathway was not observed. The current findings support the traditional use of A. altissma in phytotherapy to treat helminth infections and provide a base for standardization of the herbal material.
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Ailanthus/química , Antihelmínticos/farmacología , Caenorhabditis elegans/efectos de los fármacos , Células Germinativas/efectos de los fármacos , Extractos Vegetales/farmacología , Cuassinas/farmacología , Animales , Antihelmínticos/aislamiento & purificación , Fraccionamiento Químico , Alemania , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Corteza de la Planta/química , Cuassinas/aislamiento & purificación , Reproducción/efectos de los fármacosRESUMEN
IgE-mediated hypersensitivity reaction to pollens is a common health problem in atopic patients. In this regard, the assessment of the allergenicity of highly pollinating plants would be demanding. Based on the increment of Ailanthus altissima (A. altissima) tree in some parts of Iran and considering its probable role in respiratory allergy, in this study, we aimed to investigate its IgE-immunoreactivity and in diagnostic applications. One hundred and twenty-five allergic rhinitis patients who were diagnosed as high IgE responders and demonstrated seasonal rhinitis or rhinoconjunctivitis, as well as 20 healthy controls (HCs) with no allergic symptoms, were enrolled in this study. Total protein extract was prepared from A. altissima pollens and subjected to quality control experiments and finally used in ELISA and western blotting studies. Approximately 24% of the atopic patients (30 from 125) showed positive immunoreactivity to A. altissima extract. The median (IQR) of absorbance (450 nm) of the specific IgE against A. altissima pollen extract in HCs and positive groups were 0.33 (0.28-0.42) and 0.59 (0.36-0.79), respectively (p<0.001). Receiver operating characteristics (ROC) curve analysis of the specific ELISA results, revealed a cut-off value of 0.46 and a sensitivity of 70% and specificity of 100%. Western blotting with the sera positive cases revealed that the main immunoreactive proteins range from 10 to 70 kDa. This study revealed that some of A. altissima pollen proteins ranging from 10 to 70 kDa show IgE-reactivity in atopic patients and may play a role in their allergic reaction symptoms.
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Alérgenos/inmunología , Antígenos de Plantas/inmunología , Polen/inmunología , Rinitis Alérgica/diagnóstico , Adulto , Ailanthus/inmunología , Femenino , Humanos , Hipersensibilidad Inmediata , Inmunización , Inmunoglobulina E/metabolismo , Irán , Masculino , Extractos Vegetales , Adulto JovenRESUMEN
Seven undescribed terpenylated coumarins, named altissimacoumarin I-O, together with seven known compounds, altissimacoumarin C, altissimacoumarin E, altissimacoumarin G, altissimacoumarin H, puberulin, 7-(3-Methyl-2-butenyloxy)-6-methoxycoumarin and artelin were isolated from the root bark of Ailanthus altissima (Mill.) Swingle. Their structures were elucidated by comprehensive spectra data analysis, NMR calculation, DP4+ analysis and ACD/Structure Elucidator software simulation. The absolute configurations of altissimacoumarins K, L, M and N were determined by modified Mosher's method. All isolates were tested for their cytotoxic effect against two hepatoma carcinoma cell lines (HepG2, Hep3B). Altissimacoumarin C exhibited moderate cytotoxic effect against Hep3B cells, with IC50 of 45.21 µM.
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Ailanthus , Cumarinas , Corteza de la Planta , Extractos VegetalesRESUMEN
Ailanthone (AIT) is a quassinoid natural product isolated from the worldwide-distributed plant Ailanthus altissima. The drug displays multiple pharmacological properties, in particular significant antitumor effects against a variety of cancer cell lines in vitro. Potent in vivo activities have been evidenced in mice bearing hepatocellular carcinoma, nonsmall cell lung cancer and castration-resistant prostate cancer. This review focusses on the mechanism of action of AIT, notably to highlight the capacity of the drug to activate DNA damage responses, to inhibit the Hsp90 co-chaperone p23 and to modulate the expression of several microRNA. The interconnexion between these effects is discussed. The unique capacity of AIT to downregulate oncogenic miR-21 and to upregulate the tumor suppressor miRNAs miR-126, miR-148a, miR-195, and miR-449a is presented. AIT exploits several microRNAs to exert its anticancer effects in distinct tumor types. AIT is one of the rare antitumor natural products that binds to and strongly inhibits cochaperone p23, opening interesting perspectives to treat cancers. However, the toxicity profile of the molecule may limit its development as an anticancer drug, unless it can be properly formulated to prevent AIT-induced gastro-intestinal damages in particular. The antitumor properties of AIT and analogs are underlined, with the aim to encourage further pharmacological studies with this underexplored natural product and related quassinoids. HIGHLIGHTS: Ailanthone (AIT) is an anticancer quassinoid isolated from Ailanthus altissima It inhibits proliferation and induces cell death of many cancer cell types The drug activates DNA damage response and targets p23 cochaperone Up or downregulation of several microRNA by AIT contributes to the anticancer activity Analogs or specific formulations must be developed to prevent the toxicity of AIT.
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Ailanthus/química , Antineoplásicos Fitogénicos/farmacología , Cuassinas/farmacología , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones , MicroARNs/genética , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Cuassinas/aislamiento & purificación , Cuassinas/uso terapéuticoRESUMEN
The reduction of synthetic chemistry use in modern viticulture relies on either the biological control of microorganisms or the induction of pathogenesis-related proteins. In the present study, the effects of hydro-alcoholic plant extracts (PEs) (i.e., by-products of Vitis vinifera L., leaves of Olea europaea L. and Ailanthus altissima (Mill.) Swingle) were tested on purified enzymes activity involved in plant-pathogen interactions. The polyphenolic composition was assayed and analyzed to characterize the extract profiles. In addition, suspension cell cultures of grapevine were treated with PEs to study their modulation of chitinase activity. Application of grape marc's PE enhanced chitinase activity at 4 g L-1. Additionally, foliar treatment of grape marc's PE at two doses (4 g L-1 and 800 g L-1) on grapevine cuttings induced a concentration-dependent stimulation of chitinase activity. The obtained results showed that the application of bioactive compounds based on PEs, rich in phenolic compounds, was effective both at in vitro and ex/in vivo level. The overall effects of PEs on plant-pathogen interaction were further discussed by applying a multi-criteria decision analysis, showing that grape marc was the most effective extract.
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Quitinasas/metabolismo , Extractos Vegetales/análisis , Proteínas de Plantas/metabolismo , Polifenoles/análisis , Vitis/metabolismo , Ailanthus/química , Células Cultivadas , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Olea/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Polifenoles/farmacología , Vitis/efectos de los fármacosRESUMEN
Ailanthus altissima Swingle is a deciduous tree, belonging to the Simaroubaceae family. Phytochemical investigation of the root barks of A. altissima showed the presence of eight pairs of enantiomeric 8,4'-type oxyneolignans (1a/1b-8a/8b) including nine undescribed compounds (1b, 2a, 3a/3b, 4a/4b, 5b, 7b, 8a). Their structures were elucidated by comprehensive spectroscopic analyses, and their absolute configurations were determined by comparison of the experimental and quantum chemical calculations of electronic circular dichroism (ECD) curves. In addition, their neuroprotective effects against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells were investigated. Among them, 4a, 4b, and 8b exhibited moderate neuroprotective activity.
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Ailanthus/química , Lignanos/farmacología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Línea Celular Tumoral , China , Humanos , Peróxido de Hidrógeno , Lignanos/aislamiento & purificación , Estructura Molecular , Neuroblastoma , Fármacos Neuroprotectores/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Corteza de la Planta/química , Raíces de Plantas/química , EstereoisomerismoRESUMEN
The Ailanthus altissima pollen (AAP) has been reported as an emerging aeroallergen worldwide. This paper aims at examining the allergen pattern and the elemental composition of A. altissima pollen collected during two consecutive seasons (2014 and 2015). A gel-based allergomic study and SEM coupled to energy-dispersive X-ray (EDX) analysis have been carried out in order to evaluate the allergenic and elemental composition of AAP in two consecutive years. The IgE reactive patterns of 2014 and 2015 AAP PBS extracts were compared using the serum of a 31-year-old woman suffering from severe pollinosis symptoms to AAP. The EDX analysis revealed an important year-to-year variation in the ratios of some polluting elements such as nickel, sulfur, aluminum, lead, and copper. Gel alignments and comparative immunoproteomic analyses showed differential protein expression and IgE reactive patterns between AAPs collected in 2014 and 2015 pollinating seasons. From 20 distinct IgE-reactive spots detected in AAP extracts, 13 proteins showed higher expression in 2014 sample, while 7 allergen candidates exhibited an increased expression in AAP collected in 2015. Matrix-assisted laser desorption ionization-MS/MS analyses led to the identification of 13 IgE-binding proteins with confidence, all belonging to well-known allergenic protein families, i.e., enolase, calreticulin, and pectate lyase. Overall, the 2014 AAP showed higher concentrations of urban polluting elements as well as an increased expression of allergenic pectate lyase isoforms of about 52 kDa. This study demonstrates that the implementation of allergomic tools for the safety assessment of newly introduced and invasive plant species would help to the comprehensive monitoring of proteomic and transcriptomic alterations involving environmental allergens.
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Ailanthus/química , Contaminantes Atmosféricos/análisis , Alérgenos/análisis , Monitoreo del Ambiente , Polen/química , Adulto , Contaminación del Aire/estadística & datos numéricos , Femenino , Humanos , Proteínas de Plantas/análisis , Polisacárido Liasas , Proteómica , Rinitis Alérgica Estacional/epidemiología , Espectrometría de Masas en TándemRESUMEN
This study aimed to identify the physicochemical and the chemical properties of Ailanthus altissima (Miller) Swingle seed oil and to evaluate its in vitro antioxidant and antibacterial activities and in vivo analgesic and anti-inflammatory activities. The fatty acids' composition was determined using GC-FID. The oil was screened for antioxidant activity by DPPH test. The analgesic and anti-inflammatory activities were determined using the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats, respectively. Volatile compounds were characterized by HS-SPME-GC-MS. A. altissima produces seeds which yielded 17.32% of oil. The seed oil was characterized by a saponification number of 192.6 mg KOHâg of oil, a peroxide value of 11.4 meq O2âkg of oil, a K232 of 4.04, a K270 of 1.24, and a phosphorus content of 126.2 ppm. The main fatty acids identified were palmitic (3.06%), stearic (1.56%), oleic (38.35%), and linoleic acids ones (55.76%). The main aroma compounds sampled in the headspace were carbonyl derivatives. The oil presents an important antioxidant activity (IC50 = 24.57 µg/mL) and a modest antimicrobial activity. The seed oil at 1 g/kg showed high analgesic (91.31%) and anti-inflammatory effects (85.17%). The presence of high levels of unsaturated fatty acids and the noteworthy antioxidant capacity of the seed oil can hypothesize its use as an analgesic and anti-inflammatory agent.
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Ailanthus/química , Aceites de Plantas/química , Analgésicos/análisis , Animales , Antioxidantes/farmacología , Bencenosulfonatos , Cromatografía de Gases , Edema/inducido químicamente , Ácidos Grasos/análisis , Cromatografía de Gases y Espectrometría de Masas , Aceites de Plantas/farmacología , Ratas , Semillas/efectos de los fármacosRESUMEN
BACKGROUND: Murine models have been widely used in the study of allergy as sensitized mice can produce IgE and/or IgG1in response after the injection of an antigen/adjuvant combination. Ailanthus altissima pollen (AAP) has been recently reported as an emerging aeroallergen in Iran. So far, several AAP candidate allergens by the screening of allergen-specific IgE in the sera from AAP sensitized patients in Iran. OBJECTIVE: The aim of the present study was to detect and compare the allergens eliciting an IgE response in a mouse model, and in human, using pollen extract of A. altissima and an immunoproteomics based approach. METHODS: The pollen proteins were extracted in phosphate-buffered saline (PBS). Thirty male BALB/c mice were randomly divided into two groups of AP extract sensitized and sham that respectively received AAP PBS extract and a PBS control by intraperitoneal injections at regular intervals. The optimized AAP protein extracts were analyzed using 2D-gel electrophoresis and were subsequently confronted to pooled sera of sensitized mice. RESULTS: Two-D gel electrophoresis of AAP extract allowed the separation of 125 protein spots distributed in a wide range of pI and molecular masses. Two-DE immunoblotting using pooled sera of sensitized mice led to the detection of 14 IgE reactive spots with molecular masses ranging from 12 to 40-42kDa. CONCLUSION: The results do not correlate with our previous analyses using human AAP-sensitized sera. These findings reflect some differences in the sIgE reactivity to allergenic proteins in animal models.